Moderate Alcohol Consumption, Fat and Carbohydrate Metabolism and Insulin Sensitivity

The Effect of Moderate Alcohol Consumption on Markers of Oxidative Phosphorylation and Lipid Oxidation and on Postprandial Glycemic Control in Healthy, Lean and Overweight, Young Men

Moderate alcohol consumption is associated with a decreased risk of diabetes type 2. This association could be mediated by an improvement of insulin sensitivity with moderate alcohol consumption. Patients with diabetes type 2 or impaired glucose tolerance often may have decreased fat oxidative capacity or oxidative phosphorylation in tissue such as muscle. This could lead to accumulation triglyceride storage in muscle, which could interfere with insulin signaling. Whether such mechanism can also play a role with moderate alcohol consumption is unknown and will be investigated in this study. In addition, moderate alcohol consumption with a meal can lead to delayed hypoglycemia in type 1 diabetes patients. How moderate alcohol consumption affects postprandial glycemic response in healthy subjects is unknown. This is a secondary objective of this trial.

To investigate the effect of moderate alcohol consumption on enzymes involved in fatty acid oxidation, oxidative phosphorylation and glycolysis in skeletal muscle transporters of fatty acids and glucose in fat tissue post-prandial glycemic response in healthy, lean or overweight, young men Design : Open, randomized, partially diet-controlled, placebo controlled cross-over design Participants Description : Healthy, lean and overweight young (18-40 years) men Number : 20 Study substances Test substance : 100 ml whiskey (Famous Grouse, 40% v/v alcohol: ≈ 32 g alcohol) Reference substance : 100 ml mineral water (Spa blauw) Duration: 2 treatment periods of 4 weeks (28 days) Test parameters: Muscle biopsy for activity of 3-hydroxy fatty-acyl CoA dehydrogenase, citrate synthase, cytochrome c oxidase Postprandial glycemic response (glucose, insulin, GLP-1, GLP-2, GIP, glucagon, FFA etc.) Insulin sensitivity and related factors (oral glucose tolerance test, adiponectin, HbA1c) Liver enzymes (safety) Body weight Urinary ethyl glucuronide (compliance)

Moderate alcohol consumption, Fat and carbohydrate oxidative capacity, Postprandial glycemic response

enzymes involved in fatty acid oxidation, oxidative phosphorylation and glycolysis in skeletal muscle

Inclusion Criteria: Healthy men aged between 18 and 40 years Lean subjects BMI 18.5-25 kg/m2 and overweight/obese subjects BMI >27 kg/m2 (including 18.5, 25 and 27) Alcohol consumption between 7 and 28 units/week (including 7 and 28) Exclusion Criteria: Smoking Family history of alcoholism History of medical or surgical events that may significantly affect the study outcome, particularly metabolic or endocrine disorders and gastrointestinal disorders Recent blood donation More than 8 hours/week of intense exercise Blood haemoglobin concentration below 8.4 mmol/l Allergic to betadine or lidocaine.

Beulens JW, van Loon LJ, Kok FJ, Pelsers M, Bobbert T, Spranger J, Helander A, Hendriks HF. The effect of moderate alcohol consumption on adiponectin oligomers and muscle oxidative capacity: a human intervention study. Diabetologia. 2007 Jul;50(7):1388-92. doi: 10.1007/s00125-007-0699-8. Epub 2007 May 11.